Diagnostic accuracy of cell-free DNA-based non-invasive prenatal testing for fetal aneuploidies: a systematic review

Through a more precise and safer means of diagnosing foetal aneuploidies, non-invasive prenatal testing (NIPT) with cell-free DNA (cfDNA) has revolutionized prenatal screening and removed the necessity of invasive diagnostic procedures. The aim of the systematic review was to determine the limits of, diagnostic accuracies, and clinical value of cfDNA-based NIPT in different foetal aneuploidies.

We conducted a systematic review of studies assessing the diagnostic performance of cfDNA-based NIPT for detecting Trisomy 21 (T21), Trisomy 18 (T18), Trisomy 13 (T13), sex chromosome aneuploidies (SCA), and copy number variations (CNVs)The studies included were prospective, retrospective, or diagnostic accuracy studies that compared cfDNA results with invasive prenatal diagnostic tests, including amniocentesis, CVS, karyotyping, and chromosomal microarray analysis (CMA).

The number of studies reviewed was 20, and it involved a total of more than 67,500 individuals. NIPT utilizing cfDNA has proven sensitive and specific in T21, T18, and T13 and an excellent accuracy level in most risk populations. In the case of T21 there was 100% sensitivity and 100% specificity of cfDNA in various studies. For Trisomy 18 the sensitivity was between 92.3% to 100% with a high mean specificity of 99.6%-100%. The sensitivity was also good, with Trisomy 13 diagnostic performance, as it lies between 78.6% and 100% and a specificity of 99.8 to 100 percent. However, SCA and CNVs showed more variable performance with a sensitivity of between 75 to 100 per cent in SCA and between 53.6 and 97.7 per cent, respectively. The presence of discordant outcomes, particularly in relation to SCA and microdeletions, was a problem area and underscored the importance of genetic counseling and standardized procedures.

cfDNA-based NIPT is a highly effective and non-invasive tool for screening common trisomies but has limitations in detecting SCA and CNVs. While the screening's integration into clinical practice is beneficial, it is essential to address the limitations of discordant results and the psychological impacts on patients.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261277611, identifier CRD420261277611.